[Jim West Note: "Gastro-Enteritis" is the
fundamental symptom of non-paralytic poliomyelitis, i.e., the early phase of
(potentially) paralytic poliomyelitis. At the original date of this publication,
March, 1949, DDT production in the U.S. was skyrocketing, warnings from the FDA
and NIH were being ignored, and an avalanche of media hype was promoting DDT.]

During a period of more than two years, numerous cases of a curious symptom
complex, apparently never before reported, have been observed throughout the
United States. For want of a satisfactory explanation for this ailment, it has
been widely attributed to infection with a thus far illusory “virus X".

The syndrome consists of a group of or all the following Acute
gastroenteritis occurs, with nausea, vomiting, abdominal pain, and diarrhea
usually associated with extreme tenesmus. Coryza, cough and persistent sore
throat are common, often followed by a persistent or recurrent feeling of
constriction or a “lump” in the throat; occasionally the sensation of
constriction extends substernally and to the back, and may be associated with
severe pain in either arm. In some cases the hyoid bone becomes acutely painful
to pressure for a few days. Pain in the joints, generalized muscle weakness and
exhausting fatigue are usual; the latter are often so severe in the acute stage
as to be described by some patients as “paralysis.” Sometimes the initial attack
is ushered in by vertigo and syncope. Intractable headache and giddiness are not
uncommon. Occasionally herpes zoster appears. Paresthesias of various kinds
occur in most of the cases; areas of skin become exquisitely hypersensitive and
after a few days this hyperesthesia disappears only to recur elsewhere, or
irregular numbness, tingling sensations, pruritus or formication may occur.
Erratic fibrillary twitching of voluntary muscles is common. Usually there is
diminution of vibratory sense in the extremities.

After subsidence of the acute attack, irregular spasm of smooth muscle
throughout the gastrointestinal tract often persists for weeks or months,
associated with increased fatigability, which only gradually regresses. Febrile
reactions occur occasionally during the initial stages but are not the rule.
Except for a tendency to anemia, and in some cases a relative lymphocytosis, no
constant changes are observable in the blood. Many of the patients have an acute
bout of apprehension associated with the foregoing symptom complex and rarely is
this relieved by reassurance as to the absence of physical findings sufficient
to account for the severity of the disturbance.

Most striking about the syndrome is the persistence of some of the symptoms,
the tendency to repeated recurrence of others over a period of many months (some
patients fail to show complete recovery even after a year) and the lack of
detectable lesions sufficient to account for the severity of the subjective
reaction.

The high incidence, the usual absence of a febrile reaction, the persistence
and erratic recurrence of the symptoms, the lack of observable inflammatory
lesions, and the resistance even to palliative therapy, suggested an
intoxication rather than an infection. Investigation for possible etiologic
agents soon led to consideration of DDT (2, 2 bis (para-chlorophenyl) 1, 1,
1-trichloroethane; less precisely designated dichlorodiphenyltrichloroethane).
The epidemic first appeared at about the time DDT came into widespread use by
the civilian population. The signs and symptoms described in the pharmacologie
and toxicologic literature as characteristic of DDT poisoning, are identical
with those appearing in patients with the affection described (1 to 13).

Thus, among the disturbances which occur in known clinical poisoning with DDT
are the following: acute gastroenteritis with nausea, vomiting, and abdominal
pain, and diarrhea, coryza, cough, conjunctival irritation, a feeling of
constriction in the throat and chest, dyspnea, persistent sore throat,
giddiness, anxiety and apprehension, extreme lassitude, muscle weakness,
fibrillary, spastic and even convulsive contractions of voluntary muscles,
heaviness and aching of extremities, pain in joints, dermatitis, anemia, changes
in the white blood cells and increase in blood calcium. In fatal cases of
clinical DDT poisoning, tissue changes identical with those found in
experimental poisoning in animals have been reported: degenerative changes in
liver, kidney, spleen and adrenals, gastritis and enteritis with petechial
hemorrhages throughout the gastrointestinal tract and hyperplastic changes in
lymphoid follicles and Peyer’s patches; pulmonary edema, bronchopneumonia, and
changes in the blood vessels and cardiac musculature have also been reported.

Despite the fact that DDT is a highly lethal poison for all species of
animals, the myth has become prevalent among the general population that it is
safe for man in virtually any quantity. Not only is it used in households with
reckless abandon) so that sprays and aerosols are inhaled, the solutions are
permitted to contaminate the skin, bedding and other textiles are saturated, and
food and food utensils are contaminated but DDT is also widely used in
restaurants and food processing establishments and as an insecticide on crops.
Cattle, sheep and other food animals are extensively dusted with it and large
areas are indiscriminately sprayed from airplanes for mosquito control. DDT is
difficult and usually completely impossible to remove from contaminated foods
(it is not affected by cooking) (14), and it accumulates in the fat and appears
in the milk of animals who feed on sprayed pasture or on contaminated fodder or
who lick the DDT from their hides (14, to 16). As DDT is a cumulative poison (in
animals repeated small doses are as lethal as single large ones) (17, to 20) it
is inevitable that large scale intoxication of the American population would
occur. In 1944, Smith and Stohlman (17) of the National Institute of Health,
after an extensive study on the cumulative toxicity of DDT., pointed out, “The
toxicity of DDT combined with its cumulative action and absorbability from the
skin places a definite health hazard on its use.”

Since low grade chronic intoxications from small amounts in foods are
extremely difficult, if not impossible to trace, an effort was made to determine
whether severe acute attacks of the type described could be related to known
exposure to DDT. Patients complaining of the acute symptoms were therefore
questioned as to prior exposure to this agent. A few illustrative cases are
presented briefly:

Two patients developed acute gastroenteritis while at a vacation resort where
kitchen and dining room were treated to frequent doses of DDT with an
electric-powered aerosol device. in one of these patients, coryza and acute
spasm of the lumbar musculature occurred at the same timed This was followed by
a persistent sense of constriction and a feeling of a lump in the throat so
severe that investigation was made for a possible neoplasm -- none was found.
Both these patients had subsequent repeated attacks of enteritis over a period
of months and complainedof continuous extreme
fatigability, fibrillary twitching of muscles, irregular paresthesias and pain
in the extremities. Eleven months later, some of the symptoms, while
considerably less severe, were still present. One of these patients, some months
after the original attack, was unknowingly exposed directly to a DDT aerosol
used in a room connected by a partially open window with the room in which he
was working. Within an hour there was recurrence of the sense of pharyngeal and
substernal constriction, followed by nausea and abdominal discomfort. The next
day the patient had coryza and diarrhea. Subsequently, both patients were
exposed to DDT residues in an area that had been heavily sprayed. There was
severe and persistent recurrance of all the symptoms in both cases.

Twenty-five patients with the “virus X” syndrome, were exposed directly to
DDT spray or aerosol used to protect clothing from moths in a closet. In each
case, within a few hours there was coryza, cough and conjunctival irritation to
be followed next day by extreme debility, nausea, vomiting and diarrhea. The
gastroenteritis persisted in each case for from one to four weeks, and increased
fatigability, irregularly recurring malaise and other symptoms persisted for
some months.

Twelve patients slept in beds sprayed with DDT at regular intervals (purely
as a preventive measure -- none had had bedbugs). Bedding, mattress and springs
were indiscriminately saturated. All had repeated attacks of gastroenteritis
with intervening intervals in which the main complaint was a disturbing sense of
malaise. This is of interest in view of experimental poisoning in animals
produced by contact with textiles saturated with DDT (17).

Another patient made a series of airplane flights to various parts of South
America. During this trip he was repeatedly exposed to DDT aerosol used at a
number of airports to prevent international transport of mosquitoes. In each
case there was almost immediate irritation of the respiratory tract (other
passengers complained of this too), with a sense of suffocation, cough and
coryza. and giddiness. The patient’s trip had finally to he interrupted when he
developed a severe acute gastroenteritis and extreme muscular weakness requiring
bed rest for 16 days. The enteritis, for which no etiologic agent could be
found, persisted for weeks despite intensive therapy with sulfonamides,
antibiotics and adsorbing agents.

In another case, while transferring a solution of DDT in kerosene from a
spraying device to another container, the solution was spilled on the hands and
not immediately removed. A residue of the original DDT solution contaminated the
liquid subsequently used in the spraying device and to this the patient was also
exposed. Acute gastroenteritis developed the next day; this persisted for two
weeks. During this time coryza, sore throat and cough developed which subsided
three weeks later. Extreme lassitude, pain in the joints and a disturbing sense
of malaise persisted for weeks afterwards.

A patient with nutritional macrocytic anemia in whom the blood picture and
nutritional state had been maintained for many months on adequate dosage of B
vitamins, including folic acid, and liver, began to work weekends at an
institution where she also took her meals. The patient noted that she invariably
had a low grade nausea, occasional diarrhea and a sense of malaise, during and
immediately following each of these weekends, but she dismissed these symptoms
as possibly due to anxiety. When seen after several months of this regime, there
was recurrence of the anemia despite continuation of previously adequate
therapy. On inquiry it was found that the kitchen and dining room of this
institution were regularly sprayed with DDT. The patient discontinued this
employment and had no further attacks of gastritis though some malaise persisted
and the anemia responded only very slowly to more intensive therapy.

Another patient in whose home DDT sprays were regularly used, had had
repeated attacks of nausea, vomiting and diarrhea over a period of months and on
several occasions was confined to bed owing to severe pain in the joints,
muscular weakness, irregular paresthesias, and malaise. These attacks were
invariably associated with severe apprehension.

In two further cases, patients working in an establishment where stored
textiles were regularly sprayed with DOT for moth-proofing purposes, developed
repeated attacks of gastroenteritis which persisted. In each case for more than
a month and was unresponsive to any therapy. One of these patients, skeptical of
any possible connection between her previous attacks and exposure to DDT,
subsequently deliberately exposed herself to a DDT spray: nausea and severe
abdominal pain supervened within a few hours, and diarrhea occurred
subsequently. Two other skeptics who had had previous attacks of the syndrome
described, re-exposed themselves, one to skin contamination with DDT solution,
the other to DDT aerosol; both had prompt and severe recurrences which persisted
for many weeks.

Altogether data have been accumulated on more than 200 cases of the “virus X”
syndrome in which the condition followed immediately on known exposure to DDT.

On routine questioning of patients with the “virus X” syndrome as to exposure to
DDT, I was surprised to find that more than a few of them had discovered for
themselves that exposure to DDT spray or aerosol caused lachrymation, coryza,
cough, ‘wheezing” and nausea. But all of them, completely convinced of the utter
safety of DDT, dismissed these symptoms as unimportant.

As already indicated, a prominent feature in virtually all the patients was
extreme apprehensiveness. This is probably explicable on the basis of functional
and possibly even morphologic changes in the central nervous system produced by
DDT, since in DDT poisoning in animals such disturbances are frequent.* This
apprehensiveness (also reported in experimental DDT poisoning in man by
Wigglesworth (1) and by Case (2) often made care of these patients extremely
difficult since they were importunate both about (diagnosis and the demand for
relief. Infection with a hypothetical virus was distinctly unsatisfying as an
explanation and no therapy appeared in any way to modify the course of the
affection.

In some of the cases attributed to “virus X,” observed at different times in
different parts of the country, concomitant infection with actual known viruses,
such as that of influenza and the common cold, is of course possible. This may
have been responsible for failure thus far to consider the possibility basically
of a toxic rather than an infectious agent.

Discussion

The toxicology of DDT has been investigated extensively in a large number of
species (17, to 24). It has been found almost without exception to be lethal to
every form of animal life tested, the only limiting feature being the waxy
nature of DDT and its solubility only in lipoids and lipoid solvents. It is
largely this limited solubility which has been depended on (excessively, it now
appears) to safeguard man and other mammals from poisoning.

In rats, mice, rabbits, guinea pigs, cats, dogs, chicks, goats, sheep,
cattle, horses and monkeys, DDT produces functional and degenerative changes in
the liver, gall bladder, kidney, spleen, thyroid, adrenals, ovaries, myocardium,
voluntary musculature, central nervous system and peripheral nerves,
gastrointestinal tract and blood (with variations depending on the species) (17
to 24). DDT is as lethal in repeated small doses as in larger single doses. In
low-grade chronic poisoning in animals growth is impaired (20). The severe liver
damage that results in these animals is not affected either by adequate protein
(17) or by choline (20). In chronic administration by mouth no difference in
toxicity is detectable between use of DDT in oil solution or in dry form (20).
In chronic intoxication in rats there is a tendency to tumor formation in the
liver (20). DDT is stored in :the body fat and is excreted in the milk of dogs,
rats, goats and cattle (15, 16).

Following an initial peak, excretion of DDT in the urine reaches a plateau
and continues thereafter at a slow rate (18, 25) ; thus cumulative poisoning
with DDT can and undoubtedly does occur with ease. DDT is demonstrable in the
blood, bile, liver, kidney and central nervous system, as well as in the urine,
in both acute and chronic poisoning (17), (despite imperfect absorption. In
cattle, eating of fodder contaminated with DDT residues in very small amounts,
leads to storage in the muscles in amounts chemically detectable five weeks
after discontinuing ingestion of DDT (14). Therefore, in addition to direct
exposure to DDT powders, sprays and aerosols, cumulative poisoning in human
beings is possible from ingestion of meat, milk, butter and other foods
contaminated with traces of DDT.

Based partly on the military use of DDT, partly on acute studies on a small
number of healthy adult volunteers and on limited observations of workers
handling DDT, the misapprehension is widely current that DDT is lethal only to
insects and is completely safe in all its forms for almost any insecticidal use
by human beings. As a source of accurate toxicologic data, the military field
experience with DDT leaves much indeed to be desired. Clinical syndromes of the
type here described are hardly treated with sympathetic attention when occurring
among soldiers in wartime. Questioning of returned veterans reveals that these
reactions actually occurred frequently among soldiers exposed to DDT, but were
invariably attributed to other causes. Unfortunately, the areas in which the
heaviest treatment with DDT was required, are also the areas in which enteric
infections especially are highly endemic.

This leaves then the investigations on human volunteers. Altogether
comprehensive reports on five adult male volunteers were found in the
literature; these volunteers were exposed to cutaneous absorption and ingestion
of DDT solutions and inhalation of DDT aerosols. Of these five, three were
investigated in Britain and two in the United States. In one case reported by
Wigglesworth (1) brief application of a solution of DDT in acetone to the skin,
led to heaviness and aching of limbs and weakness of legs, “extreme nervous
tension” and anxiety, insomnia and involuntary tremors of the whole body;
anemia, leucocytosis and temporary rise in blood calcium occurred. Bed rest was
required owing to pain in the extremities. The subject was away from work for 10
weeks and at the end of a year recovery was not yet complete.

Case (2) reports his own experience and that of a colleague, who exposed
themselves to cutaneous absorption by direct contact with walls covered with a
water-soluble paint containing two per cent of DDT and subsequently treated with
a thin film of oil to simulate service conditions in the navy:

“The tiredness, heaviness, and aching of the limbs were very real things. and
the mental state also was most distressing. Not only was a state of extreme
irritability present, but also both subjects had a great distaste for work of
any sort and a feeling of mental incompetence in tackling the simplest mental
task the joint pains were quite violent at times... Subject A. I. was so
prostrated he had to take to his bed for a day.”

Other findings were increase in erythrocyte destruction, decrease in mean
corpuscular hemoglobin, increase in reticulocytes, diminution in granulocytes
accompanied by appearance of immature leukocytes, appearance of indican in the
urine, diminution of some reflexes, and in one of the subjects, patchy
anesthesia of the skin, slight impairment of hearing and transitory yellow
vision, and muscular fibrillation. Recovery required from four to five weeks.

The American subjects were made of sterner stuff, for extensive inhalation of
DDT aerosol (and in one of the subjects, subsequent ingestion of an oil solution
of DDT), according to Neal, von Oettingen and their collaborators (26,
27), led
to no significant untoward results. But even in these subjects diminution in hemoglobin from 19 to 15.5 gm. per 100 cc. occurred in one and a decrease of
from 15 Co 13.5 gm. in the other. Temporary irritation of the conjunctivae and
respiratory tract, clumsiness and forgetfulness also occurred but these were
attributed mainly to thevehicle in which DDT was
dissolved. One of these subjects, as already indicated, twice subsequently
ingested solutions of DDT in olive oil without ill effect (25). Yet Thoungh (7)
has reported 27 cases of acute gastroenteritis with vomiting, diarrhea,
giddiness and bradycardia following ingestion of rice accidentally contaminated
with DDT powder, a form in which it is claimed to be less readily absorbed.

A survey of the literature reveals at least 46 known cases of DDT poisoning
in human beings (1 to 12 to 28 to
30 to 32). The actual total is undoubtedly
larger but indefiniteness in some of the reports does not permit of an accurate
estimate. Sources of the DDT varied from actual ingestion of lethal quantities
in solution, to exposure to DDT spray and aerosol, DDT paint and DDT residues on
food. Six of the reported cases are known to have been fatal. The course of some
of the other cases is not reported beyond the initial attack. In this
investigation another fatal case undoubtedly due to DDT came to light. A young
man who handled a large amount of DDT used mainly for dusting cattle, developed
an intractable and rapidly fatal hemorrhagic gastroenteritis and hepatitis. The
condition was attributed to an infection of unknown origin.

To anyone with even a rudimentary knowledge of toxicology, it exceeds all
limits of credibility that a compound lethal for insects, fish, birds, chickens,
rats, guinea pigs, rabbits, dogs, cats, goats, sheep. horses, cattle and monkeys
would be nontoxic for human beings. The claims made by various investigators
that DDT is safe for human beings were of course based on the assumption that
the amounts to which persons would he exposed would not exceed the then known
limits of tolerance. These limits did not take into consideration sensitization
phenomena** or the tremendously wide variation in susceptibility to such toxic
agents in the general population. Most of the exposed subjects examined have
been healthy male adults, qualifications possessed by only a portion of the
total population. But even the proposed safe limits have been exceeded.

Cameron and Burgess (33), for instance, considered solutions not to exceed
0.5 per cent of DDT safe for human use and pointed out that higher
concentrations would be dangerous. Yet not only do the commercial preparations
on the American market range mainly from three to 10 per cent, but they have
been released for indiscriminate use by the general public, who in turn have
been subjected to a barrage of dangerous misinformation on the subject. Even the
0.5 per cent solution advocated by Cameron and Burgess cannot be used safely by
untrained persons, since even this concentration may be lethal to animals (34)
and would undoubtedly be at least toxic to human beings.

Among the studies on the toxicology of DDT, two are of especial interest.
Riker and his associates (35) and Jandorf, Sarrett and Bodansky (36) have both
shown that DDT increases the oxygen consumption of body tissues. There is an
increase in the metabolic rate of DDT-treated rats resembling somewhat that
produced by the nitrophenols (35). (One cannot help but draw the analogy between
the current use of DDT and the short-lived mania for dinitrophenol a decade ago.
This substance too, on the basis of an impressive toxicologic investigation, was
thought safe in limited dosage for human beings -- until they began to develop
cataract and other serious ill effects from its use). Riker and his
collaborators (35) further pointed out the resemblance between some of the
effects of DDT produced in animals and those of paraphenylenediamine and
hydroquinone. No one nowadays would even consider the indiscriminate exposure of
the public to these compounds.

An example of current impressions about the safety of DDT for the public
appears in a recent issue of LIFE magazine. In a series of pictures DDT aerosols
are shown being applied from an airplane and by ground equipment to the grounds
of a resort, the inside of a cowbarn and a house and the like. Adults, children
and cattle are shown engulfed by the aerosol, which is implied to be harmless,
“The fog covers everything with a submicroscopic and stainless film of poison,
lethal to insects but harmless to humans, animals and food.” Indeed, a young
lady is shown holding a sandwich and drinking a beverage in the midst of the
aerosol cloud. Says LIFE, “Unlike dust or spray the fog will not contaminate
food.”

In the course of inquiries made of numerous individuals, once DDT poisoning
as a clue to the “virus X” syndrome became apparent, I was amazed to find that
many persons use DDT solutions as freely as they would a detergent, and with no
safeguards whatever to avoid personal contact. Additionally, serious illness and
death in animals exposed to DDT, in every case attributed to infection, came to
light.. Two dogs dusted with DDT acquired severe “distemper” and had to be
destroyed, in an apartment, within a few hours after the closets and their
contents were intensively sprayed with DDT, a cocker spaniel began to vomit,
developed convulsions and died the next day. Three young dogs kept in a kennel
sprayed daily with DDT developed “distemper” and died, at a time when there had
been no other cases of distemper among dogs in the neighborhood. (Hill and
Robinson (3) reported death of two bull terriers sprayed with DDT). A siamese
cat dusted with DDT developed convulsions in a few hours and died some clays
later with paralysis of the hind limbs. On a cattle ranch in which the animals
were heavily dusted with DDT, a mysterious affection caused numerous deaths in
these animals from a hemorrhagic, perforating enteritis, never before observed.
In a midwestern farming community, numerous cases of an intractable hemorrhagic
diarrhea (“black, scours”) have been occurring among cattle dusted or sprayed
with DDT, kept in barns sprayed with this agent or fed with contaminated fodder.
Many of these cattle have died. The “X disease” which (“although it started only
recently”) is reported to have caused serious losses among cattle in at least 26
states, bears a remarkable resemblance to the known effects of DDT poisoning.***

There is no question that the DDT problem requires intensive further
investigation. In the meantime, public health officials might well consider
seriously the joint statement issued in 1945 by the U. S. Army and U. S. Public
Health Service (37), While this statement is concerned primarily with mosquito
control and does not adequately cover the possibility of toxic effects to human
beings and domestic animals, the cautions there advised are relevant to all the
uses of DDT.

“Successful use of the new insecticide DDT to control insect-borne disease
among our troops overseas has brought sudden renown and notoriety to this potent
war-developed insect killer. Dramatic results of its large-scale use to control
epidemics, and the spraying of DDT from aircraft, have fired public imagination
and fostered the hasty conclusion that DDT is a complete solution to all our
insect-borne disease problems. However, it must be remembered that DDT
distributed over the countryside not only wipes out malaria-carrying mosquitoes
but also may kill other insects, many of which are beneficial. Much still must
be learned about the effect of DDT on the balance of nature, important to
agriculture and wildlife, before general outdoor application of DDT can be
safely employed in this country. It may be necessary to ignore these
considerations in war areas where the health of our fighting men is at stake,
but in the United States such considerations cannot be neglected. Extensive
investigations are now being carried out by authorized agencies to determine the
usefulness and possible hazards in the largescale dissemination of DDT. Until
more information has been obtained from such investigations and until it has
been evaluated by all interested parties, plans to employ DDT indiscriminately
for outdoor area control of insect disease vectors in this country are not to be
encouraged.”

Summary

Evidence is presented that the new syndrome widely prevalent in the United
States for more than two years and attributed to infection with a hypothetical
“virus X”, is in reality due to DDT poisoning.

Footnotes:

*Needless to say, findings related to the nervous system, and muscular spasm
and weakness in severe acute affections of this type, have led to confusion with
such entities as meningitis and poliomyelitis.**One patient, in the series reported in this paper, had been heavily exposed to
DDT spray without apparent ill effect. A year later he was again exposed and
promptly collapsed; he had nausea, vomiting, diarrhea, extreme muscular
weakness, pain and aching in the limbs, etc. See also references l1 and
32.***“X disease" of cattle is described as follows (Prairie Farmer 120:31, Aug.
28, 1948): "Young animals are most susceptible. Severely affected animals
usually die. Pregnant animals frequently abort. It lasts from several weeks to
about three months. Four to eight per cent of affected cattle die. Symptoms
include a watery discharge from the eyes and nose, failing appetite, loss of
condition, depression, and a gradual thickening of the skin. Sometimes diarrhea
occurs in the late stages.” Later reports indicate the incidence to be 31 per
cent and the mortality 59 per cent.